P1682: MTHFR C677T GENOTYPE IN CORRELATION WITH THROMBOSIS AND ASSOCIATION WITH FVIII COAGULANT ACTIVITY IN GREEK PAEDIATRIC POPULATION
Authors: S. Saslis, A. Dettoraki, Z. Kapsimali, A. Michalopoulou, S. Thymianou, M. Mazarakis, H. Pergantou
Journal: HemaSphere (2022)

Background: The polymorphism C>T substitution in position 677 (C677T) of the encoding gene of methylenetetrahydrofolate reductase (MTHFR), creates a thermolabile enzyme with reduced activity that may predispose to hyperhomocysteinemia, an established risk factor for arterial thrombosis and premature atherosclerosis and a probable risk factor for venous thromboembolic disease and its recurrence in the general population. There are conflicting results as to the role of the MTHFR C677T polymorphism as a risk factor for thrombosis. Although the homozygous substitution is often associated with hyperhomocysteinemia, mainly in folate deficiency, a clear association between this genetic marker and thrombosis has not yet been established. Aims: Primary aim was to evaluate the prevalence of mutant C677T MTHFR and its association with thrombosis in the Greek paediatric population. Secondary aim was to evaluate whether different MTHFR genotype is associated with evidence of activation of coagulation cascade through increased factor VIII activity. Methods: Data were retrospectively collected from children referred to our Haemostasis and Thrombosis Centre for laboratory screening of thrombophilia between 2018 and 2020. Some of them were checked due to history of thrombosis. Children were categorized according to MTHFR C677T genotype. FVIII Coagulant activity (%) was measured by One Stage Assay, away from acute thrombosis. The identification of mutations was based on polymerase chain reaction (PCR) and reverse- hybridization. Statistical analysis was performed with t-test and ANOVA. Results: A total of 688 children (boys: 49 %) of mean age 8.9± 8 years (0-18) were investigated. Twelve percent (81/688) of them had history of thrombosis, mainly venous thromboembolic disease. Children were categorized as follows: homozygous MTHFR C677T (15%), heterozygous (47%) and normal (38%). There was thrombosis history in 12% of homozygous MTHFR C677T, 11% heterozygous and 12 % of normal, fact showing that there is no association between MTHFR C677T genotype with thrombosis. Children with homozygosity MTHFR C677T, compared to children with heterozygosity and normal MTHFR C677T showed increased factor VIII values (132.8 vs 126.4 and 131.6, %, respectively), but without statistically significant difference. However, independently of MTHFR C677T genotype, mean factor VIII values were significantly increased in all children, with thrombosis history when they were compared to children without thrombosis history (161.3 vs 125.1, %, p<0.001). Interestingly, in children with thrombosis, mean factor VIII level was statistically increased in heterozygous and normal MTHFR C677T in contrast to children with MTHFR C677T homozygosity, in whom no statistically significant increase was found (166.9 vs 121.4, %-p<0.05, 160.2 vs 127.6, %-p<0.05 and 148.3 vs 130.6, %-p>0.05, respectively). Finally, it should be noticed that during the year 2020 mean factor VIII values were much increased in all children in comparison to the years 2018, 2019 and 2021 (137 vs 129, 123 and 127, %, respectively), probably reflecting the effects of unknown pandemic COVID-19 which initiated in 2020, and showing that factor VIII could be an evidence of stress condition. Summary/Conclusion: There is no probably association between MTHFR C677T genotype and thrombosis in our paediatric population. Moreover, it was not proved that different MTHFR genotypes affect factor VIII activity.